| Backgroud:Coronary artery disease(CAD) is one of the biggest threatens of the human beings health in 21st century. According to the NECP-ATPIII (NCEP 2002), male patients<55y and females <65y are considered premature CAD (pCAD) cases, which account for a quarter of the total CAD burden. Interleukin, one type of cytokines, have several single nucleotide polymorphism (SNP) in its promoter. These functional promoters may affect the transcriptional activity of the interleukin, thus interfere the expression of the cytokine. Numerous domestic and foreign researches have proved the connection between SNPs and the inflammatory diseases. Nevertheless, There are very few Researches focusing on the SNPs of interleukin and the progression of the CAD, especially the major adverse cardiac event (MACE). Through the analysis between the SNPs and the MACE of the patients suffering CAD may support evidences of the role of interleukin in the progression of the disease, moreover, provide the genetic basis for the screening of the high-risk population and the analysis of the prognosis. Based on that,we choose the SNPs of IL9:rs31563 C>T, IL9:rs31564 G>T, IL10:rs1800872 T>G, IL12A:rs2243115 T>G, IL12B:rs3212227 T>G, using large-sample-population epidemiological prognostic design along with the selection of the environmental risk factor, analyzing the cross function between gene-environment and gene-gene and the prognosis of the CAD patients.Objective:1、To evaluate the association between the SNPs of IL-9、IL-10、IL-1、IL-12A and IL-12B and the risk of MACE of PCAD and mature CAD;2、Using Dual-Luciferase Reporter Assay System to analyze the relationship between genetic variant and the functional meaning of the polymorphisms. Demonstrating the role SNPs playing in the increased risk of MACE of PCAD and mature CAD patients.Methods:1 A total of 754 hospitalized patients in the cardiovascular department from Zhongda hospital affiliated to Southeast University who are diagnosed as coronary heart disease based on the evidence of coronary angiography were recruited in to the study. The blood sample for DNA extraction and basic information about epidemiological data, physical examination, biochemical examination was collected from every patient. The five selected polymorphisms are genotyped. The follow-up study was designed with the end event as setting major adverse cardiovascular event. We established the data base based on the laboratory results and follow-up data. Statistical methods include frequency distribution, the median descriptive analysis, log-rank test and multivariate Cox regression.Results:IL12B rs3212227 GG genotype was associated with a significant increased risk of MACE in mature CAD patients (adjusted HR=1.33,95% CI=1.00-1.76), and the report gene assay showed that rs3212227 T>G polymorphism in 3’UTR might modulate the expression of the IL12B gene. PCAD patients with three instances of pathological damage in their coronary arteries had a higher HR of MACE than the mature CAD patients (HRpCAD vs HRmcAD=2.26 vs 1.57). History of ST-elevation MI was associated with a 105% increased risk of MACE in mature CAD patients. Multivariable Cox regression analysis revealed that pCAD patients with high levels of CRP, DM,IL9 rs31564 GT/TT, and IL10 rs 1800872 TT genotypes had a higher HR of MACE, while the elder mature CAD patients with IL12B rs3212227 GG genotype, higher levels of CRP and DM had a higher HR of MACE.Conclusion:1、Multivariable Cox regression analysis revealed that pCAD patients with high levels of CRP, DM, IL9 rs31564 GT/TT, IL10 rs1800872 TT genotypes had a higher HR of MACE, while the elder mature CAD patients with IL12B rs3212227 GG genotypes, higher level of CRP and DM had a higher HR of MACE, and the report gene assay showed that rs3212227 T>G polymorphism in 3’UTR might modulate the expression of the IL12B gene.2、Stepwise Cox proportional hazard analysis showed rs3212227 T>G variant together with age, DM, and high levels of CRP were associated with a high risk of MACE in mature CAD patients.There was no significant association between the other four SNPs and MACE risk both in the pCAD and mature CAD.3、Cox regression analysis in our study also showed that both the pCAD and mature CAD patients with the higher level of CRP (>3.90 mg/1) had a high susceptibility of the MACE. pCAD patients with DM had a worse prognosis of CAD than the mature CAD patients with DM (HRpCAD vs HRmCAD:2.863 vs 1.427), suggesting that hyperglycemia intensifies the lesion of vascular endothelial cells especially in the young CAD patients.STEMI was associated with a higher risk of MACE than NSTEMI, especially in elder CAD patients using Log-rank test,. |
PDF Full Text Request